The Requirements of Managing Phase I Clinical Trials Risks: The British and Italian Case Studies.

Phase I clinical trials represent a critical point in drug development because the investigational medicinal product is being tested in humans for the first time. For this reason, it is essential to evaluate and identify the Maximum Tolerated Dose (MTD) and the safety of the new compound. To mitigate the possible risks associated with drug administration and treatment, the European Competent Authority issued various guidelines to provide provisions and harmonize risk management processes. In the UK and Italy, particular attention should be paid to the Medicines & Healthcare Products Regulatory Agency (MHRA) phase I accreditation scheme and the specific rules set by the Italian Drug Authority through the AIFA Determination no. 809/2015. Both reference documents are based on the concept of quality risk management while conducting phase I clinical studies. Moreover, the AIFA determination outlines specific requirements for those sites that want to conduct non-profit phase I clinical trials. Indeed, the document reports peculiar activities to the "Clinical Trial Quality Team", which is a team that should support the clinical site researchers in designing, starting, performing, and closing non-profit phase I studies. In this paper, we provide a general overview of the main European guidelines concerning the management of risks during phase I trials, focusing on the main peculiarities of the schemes and rules set by the MHRA and AIFA.

Climate Change and Infectious Diseases: Navigating the Intersection through Innovation and Interdisciplinary Approaches.

The era of climate change has introduced unprecedented challenges for global public health, especially visible through the lens of infectious diseases [...].

Optimizing the Indoor Air Quality in Historical Buildings: Strategies for Environmental Improvement and Public Health Enhancement.

The endeavor to maintain and enhance the indoor air quality (IAQ) in historical buildings transcends the traditional boundaries of cultural heritage preservation, emerging as a pivotal public health concern [...].

Epidemiological and clinical analysis of exposure-related factors in non-melanoma skin cancer: A retrospective cohort study.

BACKGROUND: The incidence of non-melanoma skin cancers (NMSCs) increased over last decades, probably due to environmental concerns or to the increase of frail patients with age related comorbidities. Currently, the relationship of increasing global skin cancer rates with increased ultraviolet radiations (UVRs) resulting from stratospheric ozone depletion, global warming, and air pollution from fossil-fuel combustion. AIMS: We conducted a retrospective epidemiological study including 546 NMSC patients managed at the Dermatology Unit of the Tor Vergata Hospital to highlight different trends of sun exposure or different comorbidities. METHODS: Descriptive and inferential statistical analyses were performed to evidence differences between continous variable and Spearman rank test for dicotomical variables. Charlson Comorbidity Index was calculated to obtain the 10-years survival rate in order to identify the mean comorbidity burden of our patients. RESULTS: Considering patients with comorbidities (73.81%), actinic keratoses (AKs) was the most frequent lesion. In patients with a history of previous melanoma, basal cell carcinoma (BCC) was predominant (ANOVA test, p < 0.05) with a statistically significant correlation (rho = 0.453; p < 0.01). Squamous cell carcinoma (SCC) showed a higher rate in arterial hypertension patients, followed by the chronic heart failure and hematologic neoplasms (60%, 29.7% and 32.1%, respectively) groups. Men were more affected than women, representing 61.54% of patients. Chronic sun exposure is directly correlated with SCC rho = 0.561; p < 0.01), whereas BCC correlated with a history of sunburns (rho = 0.312; p < 0.05). CONCLUSIONS: History of photo-exposition had an important role on NMSC development especially for work or recreational reasons. Sex, age, and presence of comorbidities influenced different NMSC types. BCC was more frequent in younger patients, associated with melanoma and sunburns. The presence of SCC is associated with older patients and the hypertension group. AKs were diagnosed predominantly in oldest men, with a chronic sun-exposure history, and hematologic neoplasms group.

Re-inventing protection in a post-pandemic world: A new aerodynamic endonasal filtration technology.

Is there a "missing device" for respiratory personal protection? Does it exist an easy-to-use device, allowing extensive use in everyday settings by the population, maximizing tolerability and low visual and physical invasiveness protecting from a wide range of threats including airborne pathogens, hence including the particle range of fine and ultrafine particles? Looking at the recent past, in the urgency of finding ready-to-use solutions for the respiratory protection of the population during the outbreak of the SARS-CoV-2 pandemic, devices for occupational safety have been used, such as filtering face masks. These are devices intended for workers operating during work shifts in environments characterized by potential high risk, known a priori, often directly sensible; this makes wearers motivated to tolerate discomfort for a given period to face a localized risk, and safety managers determined to supervise compliance with usage specifications. Their use by general population has implied known shortcomings, such as weak compatibility with relational work and activities, low tolerability during prolonged use, low compliance with the proper use of the device, all of this lessening actual protection. The need for a new perspective has emerged, targeting effectiveness in whole daily life, rather than punctual efficacy. Nasal filters are promising candidates to protect individuals throughout the day during the most varied activities, but they lack a systematic definition as a device and as a product; it follows that the high complexity needed to reach an effective performance envelop is generally underestimated. By reviewing available literature, the present paper draws on the experience from the pandemic and infers systematic product specifications and characterization methods for a new, effective personal respiratory protection device; these specifications are compared with the stringent constraints associated with the endonasal applications and, based on air filtration state of the art, quantifies the need for technology disruption and outlining possible new development paths.

How Healthcare Systems Negatively Impact Environmental Health? The Need for Institutional Commitment to Reduce the Ecological Footprint of Medical Services.

The global healthcare industry plays a crucial role in preserving human health and well-being [...].

IRMA: the 335-million-word Italian coRpus for studying MisinformAtion.

The dissemination of false information on the internet has received considerable attention over the last decade. Misinformation often spreads faster than mainstream news, thus making manual fact checking inefficient or, at best, labor-intensive. Therefore, there is an increasing need to develop methods for automatic detection of misinformation. Although resources for creating such methods are available in English, other languages are often underrepresented in this effort. With this contribution, we present IRMA, a corpus containing over 600,000 Italian news articles (335+ million tokens) collected from 56 websites classified as 'untrustworthy' by professional factcheckers. The corpus is freely available and comprises a rich set of text- and website-level data, representing a turnkey resource to test hypotheses and develop automatic detection algorithms. It contains texts, titles, and dates (from 2004 to 2022), along with three types of semantic measures (i.e., keywords, topics at three different resolutions, and LIWC lexical features). IRMA also includes domainspecific information such as source type (e.g., political, health, conspiracy, etc.), quality, and higher-level metadata, including several metrics of website incoming traffic that allow to investigate user online behavior. IRMA constitutes the largest corpus of misinformation available today in Italian, making it a valid tool for advancing quantitative research on untrustworthy news detection and ultimately helping limit the spread of misinformation.

Right to Occupational Safety: Prevalence of Latent Tuberculosis Infection in Healthcare Workers. A 1-Year Retrospective Survey Carried out at Hospital of Lecce (Italy).

BACKGROUND: Prevention of latent tuberculosis infection (LTBI) in healthcare workers (HCWs) to ensure the "Right to Occupational Safety" is a special challenge globally, as HCWs have a higher risk of acquiring the infection in hospital settings because of frequent close exposure to patients suffering from tuberculosis (TB). METHODS: Aretrospective study was performed with the aim of assessing the prevalence of LTBI related to demographical and occupational risk factors among HCWs employed in a large hospital in Italy. The study involved 1461 HCWs screened for LTBI by Mantoux tuberculin skin test (TST) and then confirmed with Interferon Gamma Release Assay (IGRA) test in case of positivity. Immunosuppressed and BGC-vaccinated workers were tested directly with IGRA. RESULTS: LTBI was diagnosed in 4.1% of the HCWs and the prevalence resulted lower than other studies conducted in low TB incidence countries. The variables significantly linked with higher frequency of the infection were: age ≥40 years (OR = 3.14; 95% CI: 1.13-8.74; p < 0.05), length of service ≥15 years (OR = 4.11; 95% CI: 1.48-11.43; p < 0.05) and not being trained on TB prevention (OR = 3.46; 95% CI: 1.85-6.46; p < 0.05). Not trained HCWs presented a higher risk of LTBI also after adjustment for age and length of service, compared to trained HCWs. CONCLUSIONS: screening of HCWs for LTBI should be always considered in routinely occupational surveillance in order to early diagnose the infection and prevent its progression. Safety policies in hospital settings centered on workers' training on TB prevention is crucial to minimize LTBI occurrence in HCWs.

Scientific evidence supporting the newly developed one-health labeling tool "Med-Index": an umbrella systematic review on health benefits of mediterranean diet principles and adherence in a planeterranean perspective.

BACKGROUND: Med-Index is a one-health front-of-pack (FOP) label, based on Mediterranean diet (MedDiet) principles, developed to summarize information about the nutritional properties and related-health benefits of any food as well as its sustainable production processes, and the associated food company's social responsibility parameters in a new "Planeterranean" perspective. Thus, Med-Index can be adopted in and by any European region and authority as well as worldwide; this is achieved by consumption and cooking of locally available and sourced foods that respect MedDiet principles, both in terms of healthy nutrition and sustainable production. The huge body of scientific evidence about the health benefits of the MedDiet model and principles requires a comprehensive framework to encompass the scientific reliability and robustness of this tool. A systematic review was carried out to examine the association between human health and adherence to MedDiet patterns upon which the "Med-Index" tool was subsequently developed. METHODS: MEDLINE and PubMed databases were searched for eligible publications from 1990 to April 2023. Systematic literature reviews, with or without meta-analysis, of clinical trials and observational studies were screened by two independent investigators for eligibility, data extraction, and quality assessment. English language and the time interval 1990-2023 were applied. A registry code CRD42023464807 was generated on PROSPERO and approved for this search protocol. The corrected covered area (CCA), calculated to quantify the degree of overlap between reviews, gave a slight overlap (CCA = 4%). RESULTS: A total of 84 systematic reviews out of 6681 screened records were selected. Eligible reviews included studies with predominantly observational designs (61/84, 72.6%%), of which 26/61 referenced studies of mixed observational and RCT designs, while 23/84 (27.4%) were RCT-only systematic reviews. Seventy-nine different entries were identified for health outcomes, clustered into 10 macro-categories, each reporting a statistically significant association with exposure to the MedDiet. Adherence to MedDiet was found to strongly benefit age-related chronic diseases (21.5%), neurological disorders (19%), and obesity-related metabolic features (12.65), followed by CVDs (11.4%), cancer (10.1%), diabetes (7.5%), liver health (6.3%), inflammation (5%), mortality (5%), and renal health (1.2%). The quality of the studies was moderate to high. CONCLUSION: In the context of a "Planeterranean" framework and perspective that can be adopted in any European region and worldwide, MedDiet represents a healthy and sustainable lifestyle model, able to prevent several diseases and reduce premature mortality. In addition, the availability of a FOP, such as Med-Index, might foster more conscious food choices among consumers, paying attention both to human and planetary health.

A topic models analysis of the news coverage of the Omicron variant in the United Kingdom press.

BACKGROUND: The COVID-19 pandemic has caused numerous casualties, overloaded hospitals, reduced the wellbeing of many and had a substantial negative economic impact globally. As the population of the United Kingdom was preparing for recovery, the uncertainty relating to the discovery of the new Omicron variant on November 24 2021 threatened those plans. There was thus an important need for sensemaking, which could be provided, partly, through diffusion of information in the press, which we here examine. METHOD: We used topic modeling, to extract 50 topics from close to 1,500 UK press articles published during a period of approximately one month from the appearance of Omicron. We performed ANOVAs in order to compare topics between full weeks, starting on week 48 of 2021. RESULTS: The three topics documenting the new variant (Omicron origins, Virus mutations, News of a new variant) as well as mentions of vaccination excluding booster, Scotlands First minister statement (Communications) travel bans and mask wearing (Restrictions) and the impact of market and investing (Domains and events) decreased through time (all ps < .01). Some topics featured lower representation at week two or three with higher values before and after: Government's Scientific Advisory Group for Emergencies recommendations (Communications), Situation in the US, Situation in Europe (Other countries and regions), all ps < .01. Several topics referring to symptoms and cases-e.g., rises of infections, hospitalisations, the pandemic the holidays, mild symptoms and care; restrictions and measures-e.g., financial help, Christmas and Plan B, restrictions and New Year; and domains of consequences and events-e.g., such as politics, NHS and patients, retail sales and airlines, featured increasing representation, (all ps < .01). Other topics featured less regular or non-significant patterns. CONCLUSION: Changes in sensemaking in the press closely matched the changes in the official discourse relating to Omicron and reflects the trajectory of the infection and its local consequences.

More Children Means More Tumours? We Can Do More to Protect the Health of Our Kids-A Call for a New Epidemiology That Can Change the World.

In encyclopaedic dictionaries published until 1955, the word "tumour" was defined as an "occupational disease suffered by the workers of chemical industries", thus referring to a very specific cause [...].

Migrants' human rights and health protection during the COVID-19 pandemic in the Mediterranean Sea: what we have learnt from direct inspections in two Italian hotspots.

This study aims to assess the situation of Italian hotspots for migrant reception during the COVID-19 pandemic, and specifically analyzing the situation of two hotspots located in the Sicily Region (Pozzallo harbor and Lampedusa Island), to identify critical issues. At the same time, we hypothesize solutions to guarantee the respect of human rights and suggest an operational protocol to be applied in similar situations, considering that the migration phenomenon is increasing and involving new geographical areas. Based on data obtained through the site inspections, the facilities of Pozzallo and Lampedusa exceeded their capacity to adequately contain the spread of the SARS-CoV-2 infection. Considering these findings, we suggest a practical workflow summarizing the main actions that should be applied to contain COVID-19, or other infectious disease, spreading in hotspots for migrants. The impact of the COVID-19 pandemic on migrants has received limited attention, although the migration phenomenon did not slow down during the pandemic period. Regarding the risk of spreading infectious diseases such as COVID-19, it is necessary that those countries who are most exposed to migration flows, such as Italy, plan dedicated strategies to minimize the possibility of transmission of SARS-CoV-2, using adequate protocols to monitor the possible insurgence of variants of interest (VOIs) or variants of concern (VOCs). Finally, it is important to state that these suggestions could be applied in any future pandemics.

COVID-19 epidemic spread and green areas Italy and Spain between 2020 and 2021: An observational multi-country retrospective study.

Several studies have proposed that environmental factors influencing human wellbeing, such as chronic exposures to high levels of particulate matter, could indirectly or even directly affect also the severity of COVID-19 disease in case of infection by novel coronavirus SARS-COV2. This study has investigated the association between COVID-19 infections, hospitalizations or deaths and the extension of public green areas (km2 per 100,000 based on OECD data of 2014), an indicator that has been chosen as independent endpoint variable to test the research hypothesis in 10 Italian and 8 Spanish Provinces with more than 500.000 inhabitants, including capitals (Rome and Madrid) and bigger cities (Bologna, Catania, Florence, Genoa, Milan, Naples, Palermo, Turin and Venice for Italy; Barcelona, Valencia, Seville, Zaragoza, Malaga, Las Palmas and Bilbao for Spain). Two different methodologies have been applied: a bottom-up approach was applied to Spanish institutional data concerning contagions/hospitalizations/deaths and the extent of public green areas for each responder to an official questionnaire in the frame of a nationwide survey (with detailed data granularity per province) containing specific georeferenced information; a top-down approach was used for Italy, starting from the official figures of contagions/hospitalizations/deaths of each province and linking them to the OECD statistics about the extension of public green areas in the different areas. Linear and generalized models were used for statistical analyses including also PM2.5 in a multivariate approach (with annual average concentrations from official air quality monitoring stations) and were able to adjust for the different number inhabitants living in each province, in order to take into account the difference in contagion dynamics related to the different density of population. The results obtained for Spain are consistent with those observed for Italy, as for both countries, it has clearly emerged a statistically significant association between COVID-19 clinical features (contagions, hospitalizations, and deaths) and the extension of public green areas, as well as the annual average concentrations of PM2.5 (with this latter variable loosing statistical significance in some province). Therefore, the extension of public green areas and air pollution seem to have a high correlation with COVID-19 severity.

Incidence of Non-Melanoma Skin Cancers in Salento (Southern Italy): A 15-Year Retrospective Analysis from the Cancer Registry of Lecce.

BACKGROUND AND OBJECTIVES: Non-melanoma skin cancers (NMSCs) include basal cell carcinoma (BCC) and squamous-cell carcinoma (SCC), as well as a wide range of rare skin tumors. NMSCs is the most frequently diagnosed type of tumor among Caucasians. We aimed at estimating the incidence and mortality of NMSCs in the Salento area (Lecce province, Southern Italy), whose population is assumed to experience heavy and frequent sun exposure due to climatic/environmental factors, both for working and leisure activities. MATERIALS AND METHODS: We computed the incidence of NMSCs in the Province of Lecce by examining the comprehensive real-world data collected by the local cancer registry, which covers all the 830,000 inhabitants, over a period of fifteen years (from 2003 to 2017), with a focus on the latest 5 years (2013-2017) for the analysis of the different histologic morphologies of these tumors. The incidence of NMSCs has been described in terms of absolute frequencies, crude rates and age-adjusted direct standardized rates (DSR). Joinpoint analysis was used to examine temporal trends in the incidence of NMSCs and estimate annual percent changes (APCs). RESULTS: During the period of 2003-2017, the incidence of NMSCs reached a direct standardized rate (DSR) of 162.62 per 100,000 in men (mortality 1.57 per 100,000) and 89.36 per 100,000 in women (mortality 0.52 per 100,000), respectively. The incidence significantly increased among both men and women across the entire period. Basal cell carcinoma (BCC), with its different morphologies, represented about 67.6% of the NMSCs in men (n = 2139 out of a total of 3161 tumors observed between 2013 and 2017) and about 75.8% of the NMSCs in women (n = 1718 out of a total of 2264 tumors from 2013 to 2017), thus accounting for the vast majority of NMSCs. The results are consistent with the literature data carried out both at national and international level. CONCLUSIONS: Proper monitoring of this phenomenon through timely reporting and recording of all new NMSC cases is necessary to develop new preventive strategies.

Operative Protocol for Testing the Efficacy of Nasal Filters in Preventing Airborne Transmission of SARS-CoV-2.

BACKGROUND: Standardized methods for testing Viral Filtration Efficiency (VFE) of tissues and devices are lacking and few studies are available on aerosolizing, sampling and assessing infectivity of SARS-CoV-2 in controlled laboratory settings. NanoAg-coated endonasal filters appear a promising aid for lowering viable virus inhalation in both adult and younger populations (e.g., adolescents). OBJECTIVE: to provide an adequate method for testing SARS-CoV-2 bioaerosol VFE of bio-gel Ag nanoparticles endonasal filters, by a model system, assessing residual infectivity as cytopathic effect and viral proliferation on in vitro cell cultures. METHODS: A SARS-CoV-2 aerosol transmission chamber fed by a BLAM aerosol generator produces challenges (from very high viral loads (105 PFU/mL) to lower ones) for endonasal filters positioned in a Y shape sampling port connected to a Biosampler. An aerosol generator, chamber and sampler are contained in a class II cabinet in a BSL3 facility. Residual infectivity is assessed from aliquots of liquid collecting bioaerosol, sampled without and with endonasal filters. Cytopathic effect as plaque formation and viral proliferation assessed by qRT-PCR on Vero E6 cells are determined up to 7 days post inoculum. RESULTS: Each experimental setting is replicated three times and basic statistics are calculated. Efficiency of aerosolization is determined as difference between viral load in the nebulizer and in the Biosampler at the first day of experiment. Efficiency of virus filtration is calculated as RNA viral load ratio in collected bioaerosol with and without endonasal filters at the day of the experiment. Presence of infectious virus is assessed by plaque forming unit assay and RNA viral load variations. CONCLUSIONS: A procedure and apparatus for assessing SARS-CoV-2 VFE for endonasal filters is proposed. The apparatus can be implemented for more sophisticated studies on contaminated aerosols.

Trends of Phase I Clinical Trials in the Latest Ten Years across Five European Countries.

BACKGROUND: Phase 1 clinical trials represent a critical phase of drug development because new candidate therapeutic agents are tested for the first time on humans. Therefore, international guidelines and local laws have been released to mitigate and control possible risks for human health in agreement with the declaration of Helsinki and the international Good Clinical Practice principles. Despite numerous scientific works characterizing the registered clinical trials on ClinicalTrials.gov, the main features and trends of registered phase 1 clinical trials in Europe have not been investigated. This study is aimed at assessing the features and the temporal trend of distribution of phase 1 clinical studies, carried out in the five largest European countries over a ten-year period (2012-2021), and to evaluate the impact of the Italian regulatory framework on the activation of such studies. METHODS: The main data and characteristics of phase 1 clinical studies registered on the ClinicalTrials.gov database for France, Germany, Italy, Spain and the United Kingdom have been investigated and subsequently compared. The above-mentioned countries were selected based on similarities in terms of demographic and Gross Domestic Product (GDP) data available on official government websites. (3) Results: A total number of 6878 phase 1 clinical trials were registered for the five selected countries in the ClinicalTrials.gov database during the ten years analyzed; the studies were predominantly randomized (39.33%) and for-profit (76.64%). The most represented area of investigations was oncology (52.15%), followed by hematology (24.99%) and immunology (12.04%). The variability observed between the analyzed countries showed that the UK, Germany and France presented the highest reduction in the number of phase 1 clinical trials, while for Spain and Italy, a stable/increased trend was observed, although with a lower number of trials registered on the ClinicalTrials.gov database. (4) Conclusions: Italy displayed the lowest number of registered phase 1 clinical trials, even though it showed a stable trend over the years. In this regard, the Italian regulatory framework must urgently be adapted to that of other European countries (Spain has been the first country to implement the new Regulation (EU) No 536/2014) and streamline the process of clinical trial application to increase the attractiveness of the country. Moreover, nonprofit phase 1 clinical trials (which represent 19.81% of the total number of phase 1 clinical trials registered in Italy vs. 80.19% of profit phase 1 clinical studies) should be promoted and supported by the institutions, even from a financial point of view, to allow independent researchers to develop new therapeutic drugs.

Interconnectedness and (in)coherence as a signature of conspiracy worldviews.

Conspiracy theories may arise out of an overarching conspiracy worldview that identifies common elements of subterfuge across unrelated or even contradictory explanations, leading to networks of self-reinforcing beliefs. We test this conjecture by analyzing a large natural language database of conspiracy and nonconspiracy texts for the same events, thus linking theory-driven psychological research with data-driven computational approaches. We find that, relative to nonconspiracy texts, conspiracy texts are more interconnected, more topically heterogeneous, and more similar to one another, revealing lower cohesion within texts but higher cohesion between texts and providing strong empirical support for an overarching conspiracy worldview. Our results provide inroads for classification algorithms and further exploration into individual differences in belief structures.